earticle

영어

The capacity to mediate localized gene expression via substrate-mediated gene delivery would greatly enable numerous applications in gene therapy: i) by reducing systemic spread of vectors at the target delivery site and ii) by reducing immune responses against the vector, potentially preventing side effects in off-target regions. Immobilizing gene delivery vectors onto substrates, which serve for cell adhesion, can function to place the vectors directly inside the cellular microenvironment for subsequent cellular internalization, ultimately inducing localized gene expression adjacent to the substrate and possibly enhancing gene delivery efficiency by sustaining the contact of the vectors with target cells. Importantly, this system has the potential to reduce the vector quantities required for high level of gene expression, such that the use of lower doses can potentially reduce cellular toxicity, which is typically observed by the initial burst of gene vectors (e.g., adenoviral vectors or non-viral vectors) upon direct injection in vivo.
Due to these advantages, a variety of substrate-mediated gene delivery systems have been developed, primarily combining non-viral vectors and biomaterials. There have been few attempts to deliver viral vectors from a substrate, presumably due to the lack of moieties on the viral vectors that can specifically interact with substrates. Developing substrate-mediated delivery systems for viral vectors, however, will certainly increase the potential of the system due to substantially enhanced gene delivery capacities of viral vectors compared with non-viral vectors. We have developed a strategy to mediate immobilization of adeno-assoicated viral vectors (AAV) directly onto a substrate to which cells subsequently adhere, thus maintaining high local concentration of AAV vectors with the cell microenvironment as well as increasing the extent of physical contact with the attached cells. The development of systems with the capacity to mediate localized gene expression as well as high efficiency gene delivery will have strong potential for numerous disease therapies and tissue engineering applications.